{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T01:27:20Z","timestamp":1793582840806,"version":"4.5.0"},"reference-count":107,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"InfectoPharm Arzneimittel und Consilium GmbH, Heppenheim, Germany"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: The increasing worldwide problem of bacterial infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens has led to consideration of intravenous fosfomycin, especially in combination antimicrobial regimens. We performed a systematic review of the evidence from comparative and non-comparative studies of patients who received intravenous fosfomycin as monotherapy or in combination with other antibiotics. Methods: Relevant studies were sought in six resources (Cochrane Library, Google Scholar, PubMed Central, PubMed, Scopus, and Web of Science) and two registries [ClinicalTrials.gov and International Clinical Trials Registry Portal (ICTRP)]. Results: Of the 2351 screened articles, 53 (31 comparative and 22 non-comparative studies) reported relevant data for patients with infections at various sites caused by Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, and Gram-positive bacteria, including Staphylococcus spp. and enterococci. Intravenous fosfomycin, either as monotherapy or combination therapy, showed similar or, in some studies, better efficacy (clinical and microbiological cure) compared to therapy with antimicrobial agents not including fosfomycin. The data evaluated also suggest that intravenous fosfomycin has a good safety profile. The administration of the antibiotic may be associated with electrolyte imbalances, especially hypokalemia and hypernatremia. These adverse events may be prevented and controlled with appropriate therapeutic measures and rarely lead to the discontinuation of the drug. Conclusions: Overall, the considerable body of published data suggests that intravenous fosfomycin is safe and effective. The antibiotic may be considered for patients with both Gram-positive and Gram-negative infections, especially in critically ill patients and\/or deep-seated infections. The heterogeneity of the included studies is a limitation that prevents firm conclusions.<\/jats:p>","DOI":"10.3390\/antibiotics14121193","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"1193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Intravenous Fosfomycin for Gram-Negative and Gram-Positive Bacterial Infections: A Systematic Review of the Clinical Evidence"],"prefix":"10.3390","volume":"14","author":[{"given":"Matthew E.","family":"Falagas","sequence":"first","affiliation":[{"name":"Alfa Institute of Biomedical Sciences (AIBS), 151 23 Athens, Greece"},{"name":"School of Medicine, European University Cyprus, 2404 Nicosia, Cyprus"},{"name":"Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios S.","family":"Kontogiannis","sequence":"additional","affiliation":[{"name":"Alfa Institute of Biomedical Sciences (AIBS), 151 23 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura T.","family":"Romanos","sequence":"additional","affiliation":[{"name":"Alfa Institute of Biomedical Sciences (AIBS), 151 23 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Ragias","sequence":"additional","affiliation":[{"name":"Alfa Institute of Biomedical Sciences (AIBS), 151 23 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eleni","family":"Agoranou","sequence":"additional","affiliation":[{"name":"Alfa Institute of Biomedical Sciences (AIBS), 151 23 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stylianos A.","family":"Kakoullis","sequence":"additional","affiliation":[{"name":"School of Medicine, European University Cyprus, 2404 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.2147\/IDR.S234610","article-title":"Antimicrobial Resistance: Implications and Costs","volume":"12","author":"Dadgostar","year":"2019","journal-title":"IDR"},{"key":"ref_3","first-page":"111","article-title":"Resistance profiles of the various species of the genus Staphylococcus to 15 clinically-used antimicrobials","volume":"21","author":"Catalano","year":"1989","journal-title":"Rev. Argent. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1128\/CMR.00068-15","article-title":"Fosfomycin","volume":"29","author":"Falagas","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","first-page":"19","article-title":"Deciphering Pharmacokinetics and Pharmacodynamics of Fosfomycin","volume":"32","year":"2019","journal-title":"Rev. Esp. Quimioter."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s10096-011-1360-5","article-title":"Synergy of Fosfomycin with Carbapenems, Colistin, Netilmicin, and Tigecycline against Multidrug-Resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa Clinical Isolates","volume":"31","author":"Samonis","year":"2012","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Antonello, R.M., Principe, L., Maraolo, A.E., Viaggi, V., Pol, R., Fabbiani, M., Montagnani, F., Lovecchio, A., Luzzati, R., and Di Bella, S. (2020). Fosfomycin as Partner Drug for Systemic Infection Management. A Systematic Review of Its Synergistic Properties from In Vitro and In Vivo Studies. Antibiotics, 9.","DOI":"10.3390\/antibiotics9080500"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s00430-025-00841-3","article-title":"Synergistic Activity of Fosfomycin and Flucloxacillin against Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus: In Vitro and in Vivo Assessment","volume":"214","author":"Eberl","year":"2025","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yildiz, I.E., Mercantepe, T., Bahceci, I., Arpa, M., Batcik, S., Yildiz, Y., and Tumkaya, L. (2025). Investigation of the Effects of Fosfomycin in Kidney Damage Caused by CLP-Induced Sepsis. Life, 15.","DOI":"10.3390\/life15010002"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1093\/ckj\/sfz005","article-title":"The Renoprotective Effect of Concomitant Fosfomycin in the Treatment of Pulmonary Exacerbations in Cystic Fibrosis","volume":"12","author":"Nazareth","year":"2019","journal-title":"Clin. Kidney J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cbi.2004.05.005","article-title":"Protective Effect of Fosfomycin on Gentamicin-Induced Lipid Peroxidation of Rat Renal Tissue","volume":"148","author":"Yanagida","year":"2004","journal-title":"Chem. Biol. Interact."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.ijantimicag.2016.11.020","article-title":"Old Antibiotics for Multidrug-Resistant Pathogens: From in Vitro Activity to Clinical Outcomes","volume":"49","author":"Kaye","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/1120009X.2024.2349439","article-title":"A Comparative Study of Ceftazidime\/Avibactam-Based and Fosfomycin plus Meropenem-Based Regimens for Managing Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae in Critically Ill Patients","volume":"37","author":"Kahveci","year":"2025","journal-title":"J. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107247","DOI":"10.1016\/j.ijantimicag.2024.107247","article-title":"Intravenous Fosfomycin as Adjunctive Therapy for Gram-Negative Bacteria Bloodstream Infections: A Propensity Score Adjusted Retrospective Cohort Study","volume":"64","author":"Belati","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fois, M., De Vito, A., Cherchi, F., Ricci, E., Pontolillo, M., Falasca, K., Corti, N., Comelli, A., Bandera, A., and Molteni, C. (2024). Efficacy and Safety of Ceftazidime\u2013Avibactam Alone versus Ceftazidime\u2013Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort. Antibiotics, 13.","DOI":"10.3390\/antibiotics13070616"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jiph.2024.03.010","article-title":"Comparative Effectiveness and Mortality of Colistin Monotherapy versus Colistin-Fosfomycin Combination Therapy for the Treatment of Carbapenem-Resistant Enterobacteriaceae (CRE) Infections: A Propensity Score Analysis","volume":"17","author":"Katip","year":"2024","journal-title":"J. Infect. Public. Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107365","DOI":"10.1016\/j.ijantimicag.2024.107365","article-title":"Efficacy of Fosfomycin-Containing Regimens in Treating Severe Infections Caused by KPC-Producing Klebsiella Pneumoniae and Carbapenem-Resistant Acinetobacter Baumannii in Critically Ill Patients","volume":"64","author":"Oliva","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Assimakopoulos, S.F., Karamouzos, V., Eleftheriotis, G., Lagadinou, M., Bartzavali, C., Kolonitsiou, F., Paliogianni, F., Fligou, F., and Marangos, M. (2023). Efficacy of Fosfomycin-Containing Regimens for Treatment of Bacteremia Due to Pan-Drug Resistant Acinetobacter Baumannii in Critically Ill Patients: A Case Series Study. Pathogens, 12.","DOI":"10.3390\/pathogens12020286"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"dlac121","DOI":"10.1093\/jacamr\/dlac121","article-title":"Effect of Ceftazidime\/Avibactam plus Fosfomycin Combination on 30 Day Mortality in Patients with Bloodstream Infections Caused by KPC-Producing Klebsiella pneumoniae: Results from a Multicentre Retrospective Study","volume":"4","author":"Oliva","year":"2022","journal-title":"JAC-Antimicrob. Resist."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s40121-020-00357-8","article-title":"Efficacy of a Fosfomycin-Containing Regimen for Treatment of Severe Pneumonia Caused by Multidrug-Resistant Acinetobacter Baumannii: A Prospective, Observational Study","volume":"10","author":"Russo","year":"2021","journal-title":"Infect. Dis. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1128\/AAC.02435-13","article-title":"Preliminary Study of Colistin versus Colistin plus Fosfomycin for Treatment of Carbapenem-Resistant Acinetobacter Baumannii Infections","volume":"58","author":"Sirijatuphat","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","first-page":"429","article-title":"Clinical analysis of combined consecutive therapy with fosfomycin and sulbactam\/cefoperazone for patients with pneumonia","volume":"50","author":"Kobashi","year":"2002","journal-title":"Jpn. J. Chemother."},{"key":"ref_23","first-page":"1261","article-title":"A study on the efficacy of Cefotaxime monotherapy versus Cefotaxime combined with Fosfomycin therapy for respiratory tract infections","volume":"41","author":"Shimokata","year":"1988","journal-title":"Jpn. J. Antibiot."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/BF01644272","article-title":"Fosfomycin-Ampicillin versus Gentamicin-Ampicillin in the Treatment of Critically Ill Patients with Pneumonia","volume":"14","author":"Nissen","year":"1986","journal-title":"Infection"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1038\/s41591-023-02569-0","article-title":"Cloxacillin plus Fosfomycin versus Cloxacillin Alone for Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Randomized Trial","volume":"29","author":"Grillo","year":"2023","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s40121-022-00754-1","article-title":"The Combination of Daptomycin with Fosfomycin Is More Effective than Daptomycin Alone in Reducing Mortality of Vancomycin-Resistant Enterococcal Bloodstream Infections: A Retrospective, Comparative Cohort Study","volume":"12","author":"Tseng","year":"2023","journal-title":"Infect. Dis. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1093\/cid\/ciaa1081","article-title":"Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-Resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial","volume":"72","author":"Pujol","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","first-page":"2282","article-title":"Combination Therapy with Rifampicin or Fosfomycin in Patients with Staphylococcus aureus Bloodstream Infection at High Risk for Complications or Relapse: Results of a Large Prospective Observational Cohort","volume":"75","author":"Rieg","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.cmi.2018.01.010","article-title":"Efficacy and Safety of Fosfomycin plus Imipenem versus Vancomycin for Complicated Bacteraemia and Endocarditis Due to Methicillin-Resistant Staphylococcus aureus: A Randomized Clinical Trial","volume":"24","author":"Moreno","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0248-8663(87)80116-9","article-title":"Comparaison entre fosfomycine-p6nicilline M et. p6nicilline M-Gentamicine","volume":"8","author":"Baron","year":"1987","journal-title":"La Rev. De M\u00e9decine Interne"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/cid\/ciae197","article-title":"Fosfomycin as a Potential Therapeutic Option in Nonsevere Infections Caused by Metallo-\u03b2-Lactamase\u2013Producing Enterobacterales: Need for Evidence","volume":"80","author":"Falcone","year":"2025","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1093\/cid\/ciad725","article-title":"Clinical Features and Outcomes of Infections Caused by Metallo-\u03b2-Lactamase\u2013Producing Enterobacterales: A 3-Year Prospective Study from an Endemic Area","volume":"78","author":"Falcone","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.cmi.2025.01.007","article-title":"Effectiveness and Tolerability of Intravenous Fosfomycin in Treating Complicated Urinary Tract Infections Caused by Escherichia coli: A Prospective Cohort Study from the FOSFOMIC Project","volume":"31","author":"Aslan","year":"2025","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e2137277","DOI":"10.1001\/jamanetworkopen.2021.37277","article-title":"Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial","volume":"5","author":"Morales","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1093\/cid\/ciz181","article-title":"Fosfomycin for Injection (ZTI-01) Versus Piperacillin-Tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2\/3 Randomized Trial","volume":"69","author":"Kaye","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1007\/s40121-023-00854-6","article-title":"Cefiderocol Versus Colistin for the Treatment of Carbapenem-Resistant Acinetobacter Baumannii Complex Bloodstream Infections: A Retrospective, Propensity-Score Adjusted, Monocentric Cohort Study","volume":"12","author":"Bavaro","year":"2023","journal-title":"Infect. Dis. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.jiph.2023.06.009","article-title":"Outcome of Patients with Carbapenem-Resistant Acinetobacter Baumannii Infections Treated with Cefiderocol: A Multicenter Observational Study","volume":"16","author":"Onorato","year":"2023","journal-title":"J. Infect. Public Health"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dalfino, L., Stufano, M., Bavaro, D.F., Diella, L., Belati, A., Stolfa, S., Romanelli, F., Ronga, L., Di Mussi, R., and Murgolo, F. (2023). Effectiveness of First-Line Therapy with Old and Novel Antibiotics in Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter Baumannii: A Real Life, Prospective, Observational, Single-Center Study. Antibiotics, 12.","DOI":"10.3390\/antibiotics12061048"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e02142-21","DOI":"10.1128\/aac.02142-21","article-title":"Cefiderocol-Compared to Colistin-Based Regimens for the Treatment of Severe Infections Caused by Carbapenem-Resistant Acinetobacter Baumannii","volume":"66","author":"Falcone","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mazzitelli, M., Gregori, D., Sasset, L., Trevenzoli, M., Scaglione, V., Lo Menzo, S., Marinello, S., Mengato, D., Venturini, F., and Tiberio, I. (2023). Cefiderocol-Based versus Colistin-Based Regimens for Severe Carbapenem-Resistant Acinetobacter Baumannii Infections: A Propensity Score-Weighted, Retrospective Cohort Study during the First Two Years of the COVID-19 Pandemic. Microorganisms, 11.","DOI":"10.3390\/microorganisms11040984"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"106825","DOI":"10.1016\/j.ijantimicag.2023.106825","article-title":"Efficacy of Cefiderocol- vs Colistin-Containing Regimen for Treatment of Bacteraemic Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter Baumannii in Patients with COVID-19","volume":"62","author":"Russo","year":"2023","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1093\/cid\/ciab176","article-title":"Ceftazidime-Avibactam Use for Klebsiella Pneumoniae Carbapenemase\u2013Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study","volume":"73","author":"Tumbarello","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1007\/s40121-021-00479-7","article-title":"Ceftazidime-Avibactam in Combination with In Vitro Non-Susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study","volume":"10","author":"Zheng","year":"2021","journal-title":"Infect. Dis. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.ijantimicag.2018.09.008","article-title":"Active Monotherapy and Combination Therapy for Extensively Drug-Resistant Pseudomonas Aeruginosa Pneumonia","volume":"52","author":"Khawcharoenporn","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107134","DOI":"10.1016\/j.ijantimicag.2024.107134","article-title":"Intravenous Fosfomycin in Combination Regimens as a Treatment Option for Difficult-to-Treat Infections Due to Multi-Drug-Resistant Gram-Negative Organisms: A Real-Life Experience","volume":"63","author":"Meschiari","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"107190","DOI":"10.1016\/j.ijantimicag.2024.107190","article-title":"Intravenous Fosfomycin for Treatment of Severe Infections Caused by Carbapenem-Resistant Acinetobacter Baumannii: A Multi-Centre Clinical Experience","volume":"64","author":"Russo","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/1120009X.2022.2149186","article-title":"Efficacy and Safety of Intravenous Fosfomycin for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae","volume":"35","author":"Habibi","year":"2023","journal-title":"J. Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e20230727","DOI":"10.1590\/1806-9282.20230727","article-title":"Evaluation of the Combination Treatments with Intravenous Fosfomycin for Carbapenem-Resistant Klebsiella Pneumoniae","volume":"69","author":"Kaya","year":"2023","journal-title":"Rev. Assoc. Med. Bras."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jgar.2023.03.010","article-title":"Real-Life Experience with IV Fosfomycin in Canada: Results from the Canadian LEadership on Antimicrobial Real-Life Usage (CLEAR) Registry","volume":"33","author":"Zhanel","year":"2023","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gatti, M., Giannella, M., Rinaldi, M., Gaibani, P., Viale, P., and Pea, F. (2022). Pharmacokinetic\/Pharmacodynamic Analysis of Continuous-Infusion Fosfomycin in Combination with Extended-Infusion Cefiderocol or Continuous-Infusion Ceftazidime-Avibactam in a Case Series of Difficult-to-Treat Resistant Pseudomonas Aeruginosa Bloodstream Infections and\/or Hospital-Acquired Pneumonia. Antibiotics, 11.","DOI":"10.3390\/antibiotics11121739"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3947\/ic.2022.0098","article-title":"Prescription Pattern of Intravenous Fosfomycin in a Provincial Hospital in Thailand","volume":"54","author":"Thampithak","year":"2022","journal-title":"Infect. Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1016\/j.jiph.2021.09.025","article-title":"Efficacy and Safety of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Gram-Negative Bacterial Infections","volume":"14","author":"Abdallah","year":"2021","journal-title":"J. Infect. Public Health"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.3855\/jidc.14125","article-title":"Retrospective Evaluation of Intravenous Fosfomycin in Multi-Drug Resistant Infections at a Tertiary Care Hospital in Lebanon","volume":"15","author":"Ballouz","year":"2021","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/jac\/dky406","article-title":"Fosfomycin in Severe Infections Due to Genetically Distinct Pan-Drug-Resistant Gram-Negative Microorganisms: Synergy with Meropenem","volume":"74","author":"Oliveira","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s40121-025-01125-2","article-title":"Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study","volume":"14","author":"Bodmann","year":"2025","journal-title":"Infect. Dis. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Luciano, F., Bertolino, L., Patauner, F., Boccia, F., Gallo, R., Sommese, P., Peluso, A.M.C., Infante, O., Mercadante, S., and Delle Femine, A. (2025). Efficacy and Safety of Fosfomycin Disodium in Patients with Bacterial Infections: A Single-Center, Real-Life Clinical Study. J. Clin. Med., 14.","DOI":"10.3390\/jcm14124386"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Zerbato, V., Sanson, G., Fusaro, L., Gerussi, V., Sincovich, S., Dellai, F., Del Fabro, G., Geremia, N., Maurel, C., and Giacomazzi, D. (2025). Intravenous Fosfomycin for Difficult-to-Treat Infections: A Real-Life Multicentric Study in Italy. Antibiotics, 14.","DOI":"10.3390\/antibiotics14040401"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Anastasia, A., Bonura, S., Rubino, R., Giammanco, G.M., Miccich\u00e8, I., Di Pace, M.R., Colomba, C., and Cascio, A. (2023). The Use of Intravenous Fosfomycin in Clinical Practice: A 5-Year Retrospective Study in a Tertiary Hospital in Italy. Antibiotics, 12.","DOI":"10.3390\/antibiotics12060971"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.5005\/jp-journals-10071-23958","article-title":"A Real-World Study on Prescription Pattern of Fosfomycin in Critical Care Patients","volume":"25","author":"Zirpe","year":"2021","journal-title":"Indian. J. Crit. Care Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s15010-019-01323-4","article-title":"Current Clinical Use of Intravenous Fosfomycin in ICU Patients in Two European Countries","volume":"47","author":"Putensen","year":"2019","journal-title":"Infection"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1093\/jac\/dkac023","article-title":"Influence of Daptomycin Dose and Fosfomycin Susceptibility on Outcome of Vancomycin-Resistant Enterococcus faecium Bloodstream Infections Treated with Daptomycin and Fosfomycin Combination","volume":"77","author":"Chuang","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.eimc.2018.05.009","article-title":"Clinical Efficacy of Fosfomycin Combinations against a Variety of Gram-Positive Cocci","volume":"37","author":"Parra","year":"2019","journal-title":"Enfermedades Infecc. Y Microbiol. Cl\u00edn."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e13855","DOI":"10.1111\/cts.13855","article-title":"Mortality Factors and Antibiotic Options in Carbapenem-resistant Enterobacterales Bloodstream Infections: Insights from a High-prevalence Setting with Co-occurring NDM-1 and OXA-48","volume":"17","author":"Karnmueng","year":"2024","journal-title":"Clin. Transl. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jgar.2024.12.013","article-title":"Efficacy of High Doses of Intravenous Fosfomycin for Treatment of Urinary Tract Infection Caused by KPC Carbapenemase-Producing Klebsiella Pneumoniae: An Observational Study","volume":"41","author":"Natera","year":"2025","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3947\/ic.2020.52.4.516","article-title":"Fosfomycin Dosing Regimens Based on Monte Carlo Simulation for Treated Carbapenem-Resistant Enterobacteriaceae Infection","volume":"52","author":"Kanchanasurakit","year":"2020","journal-title":"Infect. Chemother."},{"key":"ref_66","first-page":"ciaf387","article-title":"Adjunctive Fosfomycin for the Treatment of Staphylococcus aureus Bacteremia: A Pooled Post Hoc Analysis of Individual Participant Data From 2 Randomized Trials","volume":"80","author":"Ong","year":"2025","journal-title":"Clin. Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1080\/23744235.2024.2435565","article-title":"Fosfomycin in Bacteraemic Urinary Tract Infection Due to Multidrug-Resistant Escherichia coli: Insights of Post Hoc DOOR Analysis of the FOREST Trial","volume":"57","author":"Pascual","year":"2025","journal-title":"Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Marino, A., Augello, E., Bellanca, C.M., Cosentino, F., Stracquadanio, S., La Via, L., Maniaci, A., Spampinato, S., Fadda, P., and Cantarella, G. (2025). Antibiotic Therapy Duration for Multidrug-Resistant Gram-Negative Bacterial Infections: An Evidence-Based Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26146905"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e051208","DOI":"10.1136\/bmjopen-2021-051208","article-title":"Multicentre, Randomised, Open-Label, Phase IV-III Study to Evaluate the Efficacy of Cloxacillin plus Fosfomycin versus Cloxacillin Alone in Adult Patients with Methicillin-Susceptible Staphylococcus aureus Bacteraemia: Study Protocol for the SAFO Trial","volume":"11","author":"Grillo","year":"2021","journal-title":"BMJ Open"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ijantimicag.2010.09.002","article-title":"Adverse Events Associated with Intravenous Fosfomycin","volume":"37","author":"Florent","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.cmi.2016.12.005","article-title":"Intravenous Fosfomycin-Back to the Future. Systematic Review and Meta-Analysis of the Clinical Literature","volume":"23","author":"Grabein","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1080\/14787210.2020.1754193","article-title":"Intravenous Fosfomycin for the Treatment of Patients with Central Nervous System Infections: Evaluation of the Published Evidence","volume":"18","author":"Tsegka","year":"2020","journal-title":"Expert. Rev. Anti Infect. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1093\/jac\/dkae253","article-title":"Combination Therapy with IV Fosfomycin for Adult Patients with Serious Gram-Negative Infections: A Review of the Literature","volume":"79","author":"Butler","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Tedeschi, S., Giannitsioti, E., and Mayer, C. (2025). Emerging Concepts for the Treatment of Biofilm-Associated Bone and Joint Infections with IV Fosfomycin: A Literature Review. Microorganisms, 13.","DOI":"10.3390\/microorganisms13050963"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/14787210.2021.1932463","article-title":"Intravenous Fosfomycin for the Treatment of Patients with Bone and Joint Infections: A Review","volume":"20","author":"Tsegka","year":"2022","journal-title":"Expert. Rev. Anti Infect. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1473-3099(09)70325-1","article-title":"Fosfomycin for the Treatment of Multidrug-Resistant, Including Extended-Spectrum Beta-Lactamase Producing, Enterobacteriaceae Infections: A Systematic Review","volume":"10","author":"Falagas","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.ijantimicag.2015.07.019","article-title":"The Combination of Colistin and Fosfomycin Is Synergistic against NDM-1-Producing Enterobacteriaceae in in Vitro Pharmacokinetic\/Pharmacodynamic Model Experiments","volume":"46","author":"Albur","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00228-010-0794-5","article-title":"Synergy of Fosfomycin with Other Antibiotics for Gram-Positive and Gram-Negative Bacteria","volume":"66","author":"Kastoris","year":"2010","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1093\/jac\/dkae459","article-title":"Pharmacokinetic\/Pharmacodynamic Analysis of Meropenem and Fosfomycin Combinations in in Vitro Time-Kill and Hollow-Fibre Infection Models against Multidrug-Resistant and Carbapenemase-Producing Klebsiella Pneumoniae","volume":"80","author":"Farooq","year":"2025","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.ijantimicag.2009.08.013","article-title":"Clinical Significance of the Pharmacokinetic and Pharmacodynamic Characteristics of Fosfomycin for the Treatment of Patients with Systemic Infections","volume":"34","author":"Roussos","year":"2009","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1093\/jac\/dkae111","article-title":"Population Pharmacokinetic\/Pharmacodynamic Target Attainment Analysis of IV Fosfomycin for the Treatment of MDR Gram-Negative Bacterial Infections","volume":"79","author":"Wangchinda","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ijantimicag.2009.10.019","article-title":"Antimicrobial Susceptibility of Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) Enterobacteriaceae Isolates to Fosfomycin","volume":"35","author":"Falagas","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.3201\/eid2111.150750","article-title":"Fosfomycin Resistance in Escherichia coli, Pennsylvania, USA","volume":"21","author":"Alrowais","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"107272","DOI":"10.1016\/j.ijantimicag.2024.107272","article-title":"Global Prevalence of Fosfomycin Resistance Genes fosA and fosB in Multidrug-Resistant Bacteria","volume":"64","author":"Yu","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ijantimicag.2018.09.013","article-title":"Resistance to Fosfomycin: Mechanisms, Frequency and Clinical Consequences","volume":"53","author":"Falagas","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S2666-5247(24)00026-0","article-title":"Mining Staphylococcus aureus Genomic Data for Identifying Fosfomycin Resistance Genes","volume":"5","author":"Chen","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_88","unstructured":"(2024, December 19). Risk of Bias Tools\u2014ROBINS-I V2 Tool. Available online: https:\/\/www.riskofbias.info\/welcome\/robins-i-v2."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.eimc.2022.06.004","article-title":"Executive Summary of the Consensus Document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the Diagnosis and Antimicrobial Treatment of Infections Due to Carbapenem-Resistant Gram-Negative Bacteria","volume":"41","author":"Pintado","year":"2023","journal-title":"Enfermedades Infecc. Y Microbiol. Clin. (Engl. Ed.)"},{"key":"ref_90","first-page":"Doc20","article-title":"S2k Guideline \u201cCalculated Parenteral Initial Treatment of Bacterial Infections in Adults\u2014Update 2018\u201d, 2nd Updated Version: Foreword","volume":"8","author":"Bodmann","year":"2020","journal-title":"GMS Infect. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3948","DOI":"10.1093\/eurheartj\/ehad193","article-title":"2023 ESC Guidelines for the Management of Endocarditis","volume":"44","author":"Delgado","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cmi.2021.11.025","article-title":"European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Guidelines for the Treatment of Infections Caused by Multidrug-Resistant Gram-Negative Bacilli (Endorsed by European Society of Intensive Care Medicine)","volume":"28","author":"Paul","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/S1473-3099(20)30447-3","article-title":"Defining Persistent Staphylococcus aureus Bacteraemia: Secondary Analysis of a Prospective Cohort Study","volume":"20","author":"Kuehl","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1093\/cid\/ciz257","article-title":"Defining the Breakpoint Duration of Staphylococcus aureus Bacteremia Predictive of Poor Outcomes","volume":"70","author":"Minejima","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1093\/cid\/ciac177","article-title":"How Generalizable Are Randomized Controlled Trials (RCTs) in Staphylococcus aureus Bacteremia? A Description of the Mortality Gap Between RCTs and Observational Studies","volume":"75","author":"Bai","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Asai, N., Shibata, Y., Hirai, J., Ohashi, W., Sakanashi, D., Kato, H., Hagihara, M., Suematsu, H., and Mikamo, H. (2023). A Gap of Patients with Infective Endocarditis between Clinical Trials and the Real World. J. Clin. Med., 12.","DOI":"10.3390\/jcm12041566"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1186\/s13063-015-1023-4","article-title":"A Literature Review on the Representativeness of Randomized Controlled Trial Samples and Implications for the External Validity of Trial Results","volume":"16","author":"Curtis","year":"2015","journal-title":"Trials"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijantimicag.2010.03.020","article-title":"Patients Included in Randomised Controlled Trials Do Not Represent Those Seen in Clinical Practice: Focus on Antimicrobial Agents","volume":"36","author":"Falagas","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_99","unstructured":"(2025, September 24). University of Melbourne Staphylococcus Aureus Network Adaptive Platform Trial, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05137119."},{"key":"ref_100","unstructured":"Huttner, A. (2025, September 25). Ceftazidime Plus Fosfomycin Versus Ceftazidime Alone for Severe Gram-Negative Infections: A Triple-Blind, Placebo-Controlled Point-of-Care Randomized Clinical Trial, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07063095."},{"key":"ref_101","unstructured":"Yin, M. (2025, September 25). TREAT-GNB [CR-GNB], Available online: https:\/\/clinicaltrials.gov\/study\/NCT07004049."},{"key":"ref_102","unstructured":"\u0160itum, I. (2025, September 25). Therapeutic Strategies for Carbapenem-Resistant Acinetobacter Baumannii Infections: Study Protocol, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06440304."},{"key":"ref_103","unstructured":"Salee, P. (2025, September 25). Efficacy of Colistin Monotherapy Versus Colistin Combined with Fosfomycin Against Carbapenem-Resistant Acinetobacter Baumannii Infections, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06570850."},{"key":"ref_104","unstructured":"Piconi, S. (2025, September 25). Use of Fosfomycin in the Treatment of Bacterial Infections: &quot; Real-Life&quot; Study at the ASST of Lecco, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06814899."},{"key":"ref_105","unstructured":"(2025, September 25). NeoSep1: A Study to Determine the Ranking of Existing and New Antibiotics Combinations to Treat Newborn Babies Who Are in Hospital with Severe Sepsis. Available online: https:\/\/www.isrctn.com\/ISRCTN48721236."},{"key":"ref_106","unstructured":"Trampuz, A. (2025, September 25). Efficacy and Safety of Intravenous Fosfomycin in Prosthetic Joint Infection (PJI) Caused by Staphylococci, Streptococci, Enterococci and Gram-Negative Bacilli, Including Mixed Infections and Culture Negative PJI\u2019s (\u201cPROOF-Study\u201d), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05211011."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/12\/1193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:43:48Z","timestamp":1763977428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/12\/1193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,23]]},"references-count":107,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["antibiotics14121193"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14121193","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,23]]}}}